At extremely high altitudes where mammals become cold and comatose, birds maintain their metabolism, keep warm and even fly. Hemorrhaged birds replace their blood with interstitial fluid, become extremely anemic, yet their vital signs remain normal. Few adaptations have been found to explain birds' greater hypoxia and hemorrhage endurance, especially at temperatures of -25 degrees Centigrade or below. The specific aim is therefore to test the hypothesis that specialized adaptations account for avian tolerance of hypoxia or hemorrhagic anemia in extreme cold. For example, preliminary evidence indicates that birds may use the membranes of their nasal passages to extract extra oxygen from air and to direct that oxygen preferentially to the brain with the aid of special circulatory pathways in their heads. Additional new data indicate that bird erythrocytes take up fluid and become enlarged during hypoxia. This may cause changes in the chemistry of the erythrocytes that would improve their ability to transport oxygen. Yet another possibility is that bird lungs, which are structurally and functionally different from mammal lungs, may improve their gas-exchange The proposed research is designed to confirm and investigate all of these possibilities in two species of birds, pigeons and ducks, breathing normoxic air or hypoxic air equivalent to extreme altitudes, while exposed to profound cold or thermoneutrality. Since birds tolerate blood loss that reduces their blood oxygen content to levels characteristic of high altitude, birds will also be subjected to hemorrhage as a way of making them anemic and hypoxic for comparison with birds made hypoxic by breathing hypoxic area. Birds undergo acclimational changes that affect their responses to the experimental conditions to be used in these experiments. They will therefore also be acclimated to hypoxia, to cold, or to hypoxia and cold together, for comparison with unacclimated control birds. Among the specific functions to be studied are cardiac and pulmonary mechanics, erythrocyte volume regulation and gas transport, and cerebral blood flow and oxygen delivery. The elucidation of mechanisms that confer hypoxia tolerance on birds has biomedical relevance in hemorrhage and shock, stroke, coronary artery blockage, and altitude sickness. Bird adaptations may even suggest means to improve mammalian hypoxia tolerance.